Ti Zhang1, Moustafa M Abdelaziz2, Shuang Cai3, Xinmai Yang2, Daniel J Aires4, M Laird Forrest5. 1. Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., Lawrence, KS 66047, United States. 2. Department of Bioengineering, The University of Kansas, Lawrence, KS 66045, United States. 3. Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., Lawrence, KS 66047, United States; HylaPharm LLC, Lawrence, KS 66047, United States. 4. Division of Dermatology, Department of Internal Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, United States; HylaPharm LLC, Lawrence, KS 66047, United States. 5. Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Ave., Lawrence, KS 66047, United States. Electronic address: lforrest@ku.edu.
Abstract
PURPOSE: Conventional photosensitizers for photodynamic therapy (PDT) typically have wide tissue distribution and poor water solubility. A hyaluronic acid (HA) polymeric nanoparticle with specific lymphatic uptake and highly water solubility was developed to deliver pyropheophorbide-a (PPa) for locally advanced head and neck squamous cell carcinoma (HNSCC) treatment. METHODS AND RESULTS: PPa was chemically conjugated to the HA polymeric nanoparticle via an adipic acid dihydrazide (ADH) linker. The conjugates were injected subcutaneously in a region near the tumor. Near-infrared (NIR) imaging was used to monitor distribution, and diode laser was used to activate PPa. The singlet oxygen generation efficiency of PPa was not affected by conjugation to HA nanoparticles at a PPa loading degree of 1.89 w.t.%. HA-ADH-PPa inhibited human HNSCC MDA-1986 cell growth only when photo-irradiation was applied. After HA-ADH-PPa treatment and radiation, NU/NU mice bearing human HNSCC MDA-1986 tumors showed reduced tumor growth and significantly enhanced survival time compared with an untreated group (p < 0.05). CONCLUSIONS: These results demonstrate that HA-ADH-PPa could be useful for in vivo locoregional photodynamic therapy of HNSCC.
PURPOSE: Conventional photosensitizers for photodynamic therapy (PDT) typically have wide tissue distribution and poor water solubility. A hyaluronic acid (HA) polymeric nanoparticle with specific lymphatic uptake and highly water solubility was developed to deliver pyropheophorbide-a (PPa) for locally advanced head and neck squamous cell carcinoma (HNSCC) treatment. METHODS AND RESULTS: PPa was chemically conjugated to the HA polymeric nanoparticle via an adipic acid dihydrazide (ADH) linker. The conjugates were injected subcutaneously in a region near the tumor. Near-infrared (NIR) imaging was used to monitor distribution, and diode laser was used to activate PPa. The singlet oxygen generation efficiency of PPa was not affected by conjugation to HA nanoparticles at a PPa loading degree of 1.89 w.t.%. HA-ADH-PPa inhibited human HNSCC MDA-1986 cell growth only when photo-irradiation was applied. After HA-ADH-PPa treatment and radiation, NU/NU mice bearing human HNSCC MDA-1986 tumors showed reduced tumor growth and significantly enhanced survival time compared with an untreated group (p < 0.05). CONCLUSIONS: These results demonstrate that HA-ADH-PPa could be useful for in vivo locoregional photodynamic therapy of HNSCC.
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